What Is the Value of Different Zika Vaccination Strategies to Prevent and Mitigate Zika Outbreaks?

BACKGROUND: While the 2015-2016 Zika epidemics prompted accelerated vaccine development, decision makers need to know the potential economic value of vaccination strategies. METHODS: We developed models of Honduras, Brazil, and Puerto Rico, simulated targeting different populations for Zika vaccination (women of childbearing age, school-aged children, young adults, and everyone) and then introduced various Zika outbreaks. Sensitivity analyses varied vaccine characteristics. RESULTS: With a 2% attack rate ($5 vaccination), compared to no vaccination, vaccinating women of childbearing age cost $314-$1664 per case averted ($790-$4221/disability-adjusted life-year [DALY] averted) in Honduras, and saved $847-$1644/case averted in Brazil, and $3648-$4177/case averted in Puerto Rico, varying with vaccination coverage and efficacy (societal perspective). Vaccinating school-aged children cost $718-$1849/case averted (≤$5002/DALY averted) in Honduras, saved $819-$1609/case averted in Brazil, and saved $3823-$4360/case averted in Puerto Rico. Vaccinating young adults cost $310-$1666/case averted ($731-$4017/DALY averted) in Honduras, saved $953-$1703/case averted in Brazil, and saved $3857-$4372/case averted in Puerto Rico. Vaccinating everyone averted more cases but cost more, decreasing cost savings per case averted. Vaccination resulted in more cost savings and better outcomes at higher attack rates. CONCLUSIONS: When considering transmission, while vaccinating everyone naturally averted the most cases, specifically targeting women of childbearing age or young adults was the most cost-effective.

Evaluating Vaccination Strategies for Zika Virus in the Americas.

Background: Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. Objective: To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. Design: A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. Setting: 34 countries and territories in the Americas with documented Zika outbreaks. Target Population: Males and females aged 9 to 49 years. Intervention: Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Measurements: Annual prenatal Zika infections. Results: For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Limitation: Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. Conclusion: A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. Primary Funding Source: National Institutes of Health.

Evaluating the effectiveness of localized control strategies to curtail chikungunya.

Chikungunya, a re-emerging arbovirus transmitted to humans by Aedes aegypti and Ae. albopictus mosquitoes, causes debilitating disease characterized by an acute febrile phase and chronic joint pain. Chikungunya has recently spread to the island of St. Martin and subsequently throughout the Americas. The disease is now affecting 42 countries and territories throughout the Americas. While chikungunya is mainly a tropical disease, the recent introduction and subsequent spread of Ae. albopictus into temperate regions has increased the threat of chikungunya outbreaks beyond the tropics. Given that there are currently no vaccines or treatments for chikungunya, vector control remains the primary measure to curtail transmission. To investigate the effectiveness of a containment strategy that combines disease surveillance, localized vector control and transmission reduction measures, we developed a model of chikungunya transmission dynamics within a large residential neighborhood, explicitly accounting for human and mosquito movement. Our findings indicate that prompt targeted vector control efforts combined with measures to reduce transmission from symptomatic cases to mosquitoes may be highly effective approaches for controlling outbreaks of chikungunya, provided that sufficient detection of chikungunya cases can be achieved.

Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica.

Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013-2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks.

Dengue dynamics and vaccine cost-effectiveness in Brazil.

Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses. We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials. We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58-100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US$ 534 (95% CI $369-1008) per vaccinated individual and cost-saving up to $204 (95% CI $39-678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to $237 (95% CI $159-512) and $93 (95% CI $15-368), respectively. Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.

The interactive roles of Aedes aegypti super-production and human density in dengue transmission.

BACKGROUND: A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling. METHODOLOGY/PRINCIPAL FINDINGS: Using data from seven censuses of A. aegypti pupae (2007-2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban 'patches' (1-3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R(0)) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R(0), and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities. SIGNIFICANCE/CONCLUSIONS: These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person's home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy.